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Biomedical subjects

H C Lin

Publications and source records attributed to H C Lin.

At least 361 records · Page 20Linked to original sources

Reconstitution of clathrin-coated pit budding from plasma membranes.

Receptor-mediated endocytosis begins with the binding of ligand to receptors in clathrin-coated pits followed by the budding of the pits away from the membrane. We have successfully reconstituted this sequence in vitro. Highly purified plasma membranes labeled with gold were obtained by incubating cells in the presence of anti-LDL receptor IgG-gold at 4 degrees C, attaching the labeled cells to a poly-L-lysine-coated substratum at 4 degrees C and then gently sonicating them to remove everything except the adherent membrane. Initially the gold label was clustered over flat, clathrin-coated pits. After these membranes were warmed to 37 degrees C for 5-10 min in the presence of buffer that contained cytosol extract, Ca2+, and ATP, the coated pits rounded up and budded from the membrane, leaving behind a membrane that was devoid of LDL gold. Simultaneous with the loss of the ligand, the clathrin triskelion and the AP-2 subunits of the coated pit were also lost. These results suggest that the budding of a coated pit to form a coated vesicle occurs in two steps: (a) the spontaneous rounding of the flat lattice into a highly invaginated coated pit at 37 degrees C; (b) the ATP, 150 microM Ca2+, and cytosolic factors(s) dependent fusion of the adjoining membrane segments at the neck of the invaginated pit.

Adenine Nucleotides↗

Large intestinal pH and ammonia in rats: dietary fat and protein interactions.

Mature male Sprague-Dawley rats were assigned to a 3 x 3 factorial experiment in which they were fed AIN-76A diets supplying 8, 16 and 32% of energy as protein and 12, 24 and 48% of energy as fat. During the 5 mo of feeding, 10 in vivo measurements of intracolonic pH were recorded on each rat with a flexible electrode. The pH ranged from 7.8 to 8.0 near the anus and declined to 7.4 to 7.5 at 12 cm from the anus. The mean percentages of dry matter in the contents of the colon, divided into three approximately equal segments, were as follows: proximal colon, 35; middle colon, 45; distal colon, 58. Ammonia concentrations in luminal fluid rose significantly with higher protein intake in the cecum, proximal colon and distal colon. The concentrations in the distal colon ranged from 39 to 74 mmol/L, depending upon protein intake. Thymidine incorporation by distal colon mucosal cells was higher in rats fed 32% of energy as protein and 48% of energy as fat compared with rats fed 8% of energy as protein and 12% as fat. The evidence suggests that increased intestinal cell proliferation in rats fed the high protein, high fat diet was due to greater concentrations of ammonia in the large intestine resulting from the high protein intake and greater concentrations of non-ionized ammonia resulting from the higher pH associated with increased fat intake. The actual determinations and calculations of ionized to non-ionized ammonia concentrations were compatible with the assumption that the large intestinal cells absorbed more ammonia at higher fat intakes.

Ammonia↗

Colon mucosal cell damage by ammonia in rats.

Colons of male Sprague-Dawley rats were perfused, in situ, with ammonium (NH4+) or sodium (Na+) and acetate (CH3COO-) or chloride (Cl-) to determine the effects of the cations and anions or their interactions on the colon mucosa. Solutions simulating ileal fluid were delivered at 0.4 mL/min at 38 degrees C via cannulae inserted at the cecal-colonic junction. Effluents were collected by cannulae inserted in the anus. In the first experiment, perfusion with the control solution or with the control solution having 35 mmol/L NaCl replaced by equimolar amounts of ammonium acetate, ammonium chloride or sodium acetate showed that only ammonium-containing solutions caused histological damage, loss of mucus, and significant losses of carbohydrate and DNA (P less than 0.05). The losses of carbohydrate and DNA expressed in microgram.cm-1.30 min-1 were as follows: control, 13.4 and 1.0; ammonium acetate, 31.8 and 1.6; sodium acetate, 16.0 and 0.6; ammonium chloride, 24.1 and 1.3, respectively. In the second experiment, perfusion with control fluid containing 35 or 70 mmol/L ammonium acetate at pH 6.8, 7.4 or 8.0 increased carbohydrate and DNA losses into the effluents compared with the pretest period (P less than 0.05), without significant effects related to influent pH. These studies are consistent with the concept that the life span of colon cells is shortened by concentrations of ammonia found in the colon under normal conditions and that ammonia enhances cell proliferation in the colon mucosa.

Acetates↗

Genetic organization and regulation of the xylose degradation genes in Streptomyces rubiginosus.

The xylose isomerase (xylA) and the xylulose kinase (xylB) genes from Streptomyces rubiginosus were isolated, and their nucleotide sequences were determined. The xylA and xylB genes encode proteins of 388 and 481 amino acids, respectively. These two genes are transcribed divergently from within a 114-nucleotide sequence separating the coding regions. Regulation of the xyl genes in S. rubiginosus was examined by fusing their promoters to the Pseudomonas putida catechol dioxygenase gene and integrating the fusions into the minicircle integration site on the S. rubiginosus chromosome. The expression of catechol dioxygenase was then measured under a variety of conditions. The results indicated that transcription of the xyl genes was induced by D-xylose and repressed by glucose. Data from quantitative S1 mapping were consistent with this conclusion and suggested that xylA had one and xylB had two transcription initiation sites. The transcription initiation site of xylA was 40 bp upstream of the coding region. The two transcription initiation sites of xylB were 20 and 41 bp 5' of its translation initiation codon. Under control of appropriate regulatory elements, the cloned xyl genes are capable of complementing either Escherichia coli xylose isomerase- or xylulose kinase-deficient strains. The deduced amino acid sequence of the S. rubiginosus xylA protein is highly homologous to sequences of other microbial xylose isomerases.

Aldose-Ketose Isomerases↗

Hemodynamic response of calves to tiletamine-zolazepam-xylazine anesthesia.

Six healthy Holstein calves were anesthesized with isoflurane in O2 and instrumented for hemodynamic studies. A saphenous artery was catheterized for measurement of blood pressure and withdrawal of blood for determination of the partial pressure of carbon dioxide (PaCO2), oxygen (PaO2), and arterial pH (pHa). Respiration was controlled throughout the study. The ECG and EEG were monitored continuously. A thermodilution catheter was passed via the right jugular vein into the pulmonary artery for determination of cardiac output and measurement of central venous pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure. Baseline values (time 0) were recorded following recovery from isoflurane. Tiletamine-zolazepam (4 mg/kg)-xylazine (0.1 mg/kg) were administered IV immediately after recording baseline values. Values were again recorded at 5, 10, 20, 30, 40, 50, and 60 minutes after injection. Changes in left ventricular stroke work index, PaCO2, and pHa were insignificant. Arterial blood pressure and systemic vascular resistance increased above baseline at 5 minutes and then gradually decreased below baseline at 40 minutes, demonstrating a biphasic response. Values for pulmonary capillary wedge pressure, pulmonary arterial pressure, central venous pressure, and PaO2 were increased above baseline from 5 to 60 minutes. Stroke volume, stroke index, and right ventricular stroke work index were increased from 20 or 30 minutes to 60 minutes. Pulmonary vascular resistance increased at 10 minutes, returned to baseline at 20 minutes, and was increased again at 60 minutes. Heart rate, cardiac output, cardiac index, and rate pressure product were decreased at 5 minutes, and with the exception of cardiac output, remained so for 60 minutes. Cardiac output returned to the baseline value at 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Inhibition of thromboxane formation as the antiplatelet mechanism of 3,4-dihydroxyxanthone and quercetin pentaacetate.

3,4-Dihydroxyxanthone and quercetin pentaacetate were shown to inhibit the aggregation and ATP release of washed rabbit platelets induced by collagen and arachidonic acid, but were not induced by PAF. This inhibition was reversible and in a concentration-dependent manner. The thromboxane B2 formation of washed rabbit platelets, which was caused by arachidonic acid and collagen, was also suppressed by both antiplatelet agents. In human platelet-rich plasma, 3,4-dihydroxyxanthone and quercetin pentaacetate inhibited the secondary, but not the primary aggregation induced by ADP and epinephrine. Both antiplatelet agents also inhibited collagen- and arachidonic acid-induced aggregation in whole blood in a dose-dependent manner. It is concluded that the antiplatelet effects of 3,4-dihydroxyxanthone and quercetin pentaacetate are due to the inhibition of thromboxane formation.

Adenosine Triphosphate↗

Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats.

The hemodynamic effects, including mesenteric-systemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein-stenosed rats. In rats receiving early chronic clonidine (600 micrograms.kg-1.day-1 by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 +/- 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% +/- 25%) were significantly lower than in the placebo group (15.2 +/- 1.5 mm Hg and 83% +/- 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 +/- 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% +/- 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 micrograms/kg) 10 days after portal vein stenosis, portal pressure (11.8 +/- 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% +/- 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hyposensitivity to vasopressin in patients with hepatitis B-related cirrhosis during acute variceal hemorrhage.

It has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal-hypertensive rat model. This study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 HBsAg-positive cirrhotic patients. Nine patients had active variceal hemorrhage before vasopressin infusion, and the other 16 patients were in a stable condition at the time of infusion. The two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage (96 +/- 20 vs. 73 +/- 10 beats/min, mean +/- S.D., p less than 0.01). Thirty minutes after vasopressin infusion (0.66 units/min), hepatic venous pressure gradient significantly decreased in both bleeding and stable patients (from 21 +/- 9 to 18 +/- 9 mm Hg, p less than 0.05; and from 18 +/- 4 to 8 +/- 3 mm Hg, p less than 0.0001, respectively). However, the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients (4 +/- 3 vs. 9 +/- 2 mm Hg, p less than 0.0001). A significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock (from a median of 16 mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p less than 0.05), but not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range = 18 to 33] mm Hg, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Sexual transmission of hepatitis D virus infection in Taiwan.

Multivariate analysis of the risk factors for hepatitis D virus infection among 53 men with acute hepatitis D virus superinfection, 59 men with acute exacerbation of chronic hepatitis B and 54 asymptomatic male hepatitis B carriers revealed that sexual contact with prostitutes and use of nondisposable needles were the factors significantly associated with hepatitis D virus infection in Taiwan (odds ratio = 5.5, 95% confidence interval = 3.3 to 9.2; odds ratio = 2.4, 95% confidence interval = 1.3 to 4.4, respectively). The prevalence of antibody to hepatitis D virus antigen among hepatitis B virus carriers with histories of sexual exposure to prostitutes was 10.3% (14 of 136) and the prevalence of hepatitis D virus antigen among the female prostitutes who were hepatitis B virus carriers was 59% (24 of 51). Among those who admitted to sexual contact with prostitutes, testing for hepatitis D virus antigen revealed positive correlations with the frequency of such sexual contacts and with the frequency of history of venereal diseases. Among the female prostitutes, the prevalence of hepatitis D virus antigen had a positive correlation with the frequency of sexual contact and a negative correlation with age. Analysis of serum hepatitis D virus RNA among those with hepatitis D virus antigen revealed that 4 of the 9 with sexual exposure to prostitutes and 3 of the 24 prostitutes were positive. From these findings, we conclude that these two groups are not only at high risk for hepatitis D virus infection but also form a reservoir of this virus.

Adolescent↗

Focal hepatic fatty infiltration as a cause of pseudotumors: ultrasonographic patterns and clinical differentiation.

Focal hepatic fatty infiltration may be mistaken for hepatic neoplasm on ultrasonography. A sonographic feature mimicking "space occupying lesions" was identified in 41 cases with focal fatty liver, which led to the recognition of four sonographic patterns: (1) Ten patients in whom the livers were characterized by irregular configurations of hyperechoic and hypoechoic areas. Although confusing to inexperienced sonographers, all of them were properly interpreted by experienced sonographers. (2) One patient in whom the hepatic sonography revealed a hyperechoic nodule, but which was correctly diagnosed by computed tomography (CT) scan. (3) Six patients in whom the livers were characterized by multiple confluent hyperechoic lesions, which were all misinterpreted by sonographers and misinterpreted following CT scans in 4 cases and angiography in 3 cases. (4) Twenty-four patients in whom the livers revealed focal spared areas, which was misdiagnosed by sonographers in 14 cases, but correctly diagnosed by CT scan in all 24 cases.

Adult↗

Systemic and portal haemodynamic changes following triglycyllysine vasopressin plus nitroglycerin administration in patients with hepatitis B-related cirrhosis.

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.

Adult↗

Inhibition of gastric emptying by acids depends on pH, titratable acidity, and length of intestine exposed to acid.

Exposure of the small intestine to acid inhibits gastric emptying in a dose-related fashion that depends on titratable acidity and pH. Little information is available on the location of this inhibitory mechanism or on the relative contribution of titratable acidity and pH to this feedback control. We hypothesized that the dependence on titratable acidity is related to the length of the intestine exposed to acid and that the dependence on pH is related to the region of the intestine exposed to acid. To test these ideas, we studied 11 dogs with duodenal and jejunal fistulas. The inhibitory effects were tested when different lengths of the small intestine were exposed to test solutions of 0.03, 0.06, and 0.12 meq/ml titratable acidities. pH as an independent covariable was separated from titratable acidity by comparing the inhibition of gastric emptying of lactic acid (pH fixed to 2.4) to HCl (pH 0.96-1.6). Maximal inhibition of gastric emptying by both acids depended on acid exposure of a length of small intestine that was greater than 65 but less than or equal to 150 cm long. When acid was confined to the proximal 15 cm, increasing concentration of HCl (decreasing pH) resulted in increasing inhibition, but this effect was absent with increasing concentration of lactic acid (fixed pH). Inhibition was absent when 0.06 meq/ml HCl was infused into the intestine beyond the midintestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of gastric emptying by sodium oleate depends on length of intestine exposed to nutrient.

Previously, we reported that inhibition of gastric emptying by glucose or acids depends on the length of gut exposed to the inhibitor [Gastroenterology 95: A877, 1988; Am. J. Physiol. 256 (Gastrointest. Liver Physiol. 19): G404-G411, 1989]. In this study, we hypothesized that feedback control by fat may be similarly regulated. In dogs with chronic intestinal fistulas, we compared the intensity of intestinal feedback when different lengths of the small intestine were exposed to meals of 3, 9, or 27 mM sodium oleate. We found that 1) inhibition of liquid emptying was dose dependent, 2) intensity of negative feedback was dependent on both the concentration of the oleate and the length of gut exposed to fat, 3) full inhibitory effect was achieved with exposure of fat to 150 cm of gut, 4) inhibition from the distal one-half of gut was less potent than that generated from the proximal one-half of gut, and 5) on a molar basis oleate was 20 times as effective as glucose at inhibition of gastric emptying and that this difference was related to the slower rate of fat absorption.

Animals↗

Application of a procedure starting with an HIV-I/HIV-2 mixed EIA.

A procedure to diagnose the infections by the human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) was proposed. The specimens were first screened by a mixed enzyme immunoassay (EIA) for the presence of antibodies to HIV-1 as well as to HIV-2. Those screened positive were thereafter confirmed and differentiated their antibody reactivities toward the antigens of HIV-1 and HIV-2 by Western blot (WB). This procedure was found to be one hundred percent accurate to diagnose 66 coded specimens with well defined seroreactivities to HIV-1 from Centers for Disease Control (CDC). While its accuracy in HIV-2 antibody testing could not be evaluated in the present study owing to the lack of HIV-2 standard reference specimens. With this procedure, six out of each of two groups of 176 foreigners and 719 individuals who visited the Taipei Municipal Venereal Disease Control Institute (TMVDCI) were screened repeatedly reactive by the mixed EIA. By WB only four of the first six and two of the second six were confirmed HIV-1 positive. Their antibody reactivities toward HIV-2 antigens were either absent or significantly much lower than those toward HIV-1 antigens. Furthermore, none reacted to the env proteins gp160 and gp120 of HIV-2. We therefore concluded that out of the 895 test individuals, only six were confirmed infected with HIV-1. There were neither HIV-2 infections nor dual infections. The similar pathogenicity and trans mission of HIV-2 as of HIV-1 justify an equal appreciation for HIV-2 testing. The present study indicated that a procedure starting with a mixed EIA aimed to diagnose HIV-1 as well as HIV-2 did not have any adverse effects on HIV-1 testing.

Acquired Immunodeficiency Syndrome↗

[Study on the effect of various conditions and age to blood platelet aggregation test].

The result of the platelet aggregation test was affected by various conditions. We performed the platelet aggregation test by changing different conditions, including: 1. adding different anticoagulants 2. interval between sampling and standing 3. platelet count 4. the concentrations of different reagents (ADP, Epinephrine and Collagen) respectively and the aggregation rate of blood platelet were compared among different age groups. The best condition for platelet aggregation rate was obtained as follows: 1) Citric acid of 3.8% is the best anticoagulant. 2) Test should be completed within 4 hours upon sample collection. 3) The optimal incubation temperature is between 25 degrees to 37 degrees C. 4) Platelet count of 2 to 4 x 10(5)/microliters gives the most constant result. 5) The optimal concentration for working solution of ADP, collagen and Epinephrine are 5.0 microns, 5.0 micrograms/ml and 50 microM respectively. 6) The aggregation rate of blood platelet increases with age.

Adenosine Diphosphate↗

The effects of transection of the anterior cruciate ligament on healing of the medial collateral ligament. A biomechanical study of the knee in dogs.

The effect of concurrent injury to the anterior cruciate ligament on the healing of injuries of the medial collateral ligament was studied in dogs. In Group I, isolated transection of the medial collateral ligament was performed; in Group II, transection of the medial collateral ligament with partial transection of the anterior cruciate ligament; and in Group III, complete transection of both the medial collateral ligament and the anterior cruciate ligament. The three groups of animals were examined six and twelve weeks postoperatively with respect to varus-valgus rotation of the knee and tensile properties of the femur-medial collateral ligament-tibia complex. The varus-valgus rotation of the knee was found to be the largest in Group-III specimens at all time-periods and was 3.5 times greater than the control values at twelve weeks. Group-I and Group-II specimens also showed large varus-valgus rotations at time zero, but the rotations returned to the control values by twelve weeks. For the structural properties of the femur-medial collateral ligament-tibia complex, the values for ultimate load for Groups I and II reached the control values by twelve weeks, while that for Group III remained at only 80 per cent of the control value. Both energy absorbed at failure and linear stiffness for all three groups were less than those for the controls at six weeks, and only linear stiffness returned to the control values by twelve weeks. For the mechanical (material) properties of the healed ligament substance, the values for modulus and tensile strength were markedly lower than the control values for all groups at six weeks. By twelve weeks, the tensile strength of Group-I specimens had increased to 52 per cent of the control value, while those of Groups II and III were only 45 and 14 per cent, respectively. Our results demonstrate that healing of the transected medial collateral ligament is adversely affected by concomitant transection of the anterior cruciate ligament. Both varus-valgus rotation and mechanical properties of the healed ligament failed to recover in knees that had combined transection of the anterior cruciate and medial collateral ligaments. The structural properties of the femur-medial collateral ligament-tibia complex in tension recovered more rapidly as a consequence of the large mass of reparative tissue that formed in the medial collateral ligament of the anterior cruciate-deficient knees.

Animals↗

Lack of effects of isosorbide-5-mononitrate on hepatic hemodynamics in HBsAg-positive cirrhosis.

We conducted a randomized controlled hemodynamic study to evaluate the effect of placebo and 20 mg isosorbide-5-mononitrate, a long-acting organic nitrate, in 19 patients with HBsAg-positive cirrhosis by the simultaneous measurement of portal venous pressure and wedged hepatic venous pressure. Baseline values for the two groups were similar. One hour after oral administration of 20 mg isosorbide-5-mononitrate in 10 patients, mean arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure significantly decreased from 92 +/- 13 (mean +/- S.D.) to 82 +/- 14 mmHg, from 12.9 +/- 4.5 to 9.3 +/- 2.4 mmHg and from 6.9 +/- 3.4 to 4.3 +/- 1.8 mmHg, respectively. However, both portal venous pressure gradient (from 18.1 +/- 3.6 to 17.5 +/- 3.0 mmHg) and hepatic venous pressure gradient (from 17.8 +/- 5.2 to 16.6 +/- 5.3 mmHg) remained unchanged during the study. In six patients who received 20 mg isosorbide-5-mononitrate twice daily for 7 days, hepatic venous pressure gradient remained unaltered as compared to basal and 1-hr values. There was no significant change in cardiac index, heart rate or systemic vascular resistance in either immediate (1-hr) or delayed (7-day) studies. Three patients (30%) developed mild headache or dizziness and two patients (20%) demonstrated systolic hypotension (less than mmHg) during the immediate study. This study shows that isosorbide-5-mononitrate appears to have no effect in treating portal hypertension in patients with HBsAg-positive cirrhosis. In addition, the isosorbide-5-mononitrate may affect the systemic circulation more than the portal circulation.

Aged↗

Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection.

A total of 20 patients with histologically proven primary hepatocellular carcinoma (PHC) received mitoxantrone IV at a dose of 10-16 mg/m2 every 3 weeks. All patients had previous hepatitis B infection. None underwent remission after treatment; 2 had stable disease and 18 progressive disease. The median overall survival was 13 weeks (range, 1-59 weeks). There was no evidence of significant antitumor activity for mitoxantrone in our patients with PHC. Hematotoxicity occurred in 100% of the patients with grades 2-4 leukopenia, 89% of those with grades 1-4 anemia, and 26% of those with grades 2-3 thrombocytopenia. Cardiotoxicity occurred in 20% of the patients after 14-30 mg/m2 mitoxantrone; these included complete heart block with fatal outcome in one case, decreased ventricular ejection fraction in one, and sinus tachycardia in two. Nausea, vomiting, fever, diarrhea, and alopecia were mild and occurred in 15%-45% of the patients Therefore, patients with PHC following hepatitis B infection may be less tolerant to mitoxantrone, resulting in the apparent increase in toxicities.

Adult↗